Application of the Sepsis-3 criteria to describe sepsis epidemiology in the Amsterdam UMCdb intensive care dataset.

INTRODUCTION: Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria to characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb). METHODS: We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L. RESULTS: We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,312 unique sepsis episodes, of which 30.2% met the criteria for septic shock. A total of 4,911/6,312 sepsis (77.8%) episodes occurred on ICU admission. Forty-seven percent of emergency medical admissions and 36.7% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.4%) than those without shock (11.4%). CONCLUSIONS: We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.

Bayesian model selection for multilevel models using integrated likelihoods.

Multilevel linear models allow flexible statistical modelling of complex data with different levels of stratification. Identifying the most appropriate model from the large set of possible candidates is a challenging problem. In the Bayesian setting, the standard approach is a comparison of models using the model evidence or the Bayes factor. Explicit expressions for these quantities are available for the simplest linear models with unrealistic priors, but in most cases, direct computation is impossible. In practice, Markov Chain Monte Carlo approaches are widely used, such as sequential Monte Carlo, but it is not always clear how well such techniques perform. We present a method for estimation of the log model evidence, by an intermediate marginalisation over non-variance parameters. This reduces the dimensionality of any Monte Carlo sampling algorithm, which in turn yields more consistent estimates. The aim of this paper is to show how this framework fits together and works in practice, particularly on data with hierarchical structure. We illustrate this method on simulated multilevel data and on a popular dataset containing levels of radon in homes in the US state of Minnesota.

Sepsis-3 criteria in AmsterdamUMCdb: open-source code implementation.

Sepsis is a major healthcare problem with substantial mortality and a common reason for admission to the intensive care unit (ICU). For this reason, the management of sepsis is an important area of ICU research. A number of large-scale, freely-accessible ICU databases are available for observational research and the robust identification of septic patients in such data sets is crucial for research purposes, particularly for comparative studies between critical care sub-populations which may vary around the world. However, data structures are poorly standardised due to inevitable variances in clinical electronic health record system vendor and implementation as well as research database design choices. Robust and well-documented cohort selection (such as patients with sepsis) is crucial for reproducible research. In this work, we operationalise the Sepsis-3 definition on the AmsterdamUMCdb, a recently published large European ICU database, publishing open-access code for wider use by critical care researchers.

Causality indices for bivariate time series data: A comparative review of performance.

Inferring nonlinear and asymmetric causal relationships between multivariate longitudinal data is a challenging task with wide-ranging application areas including clinical medicine, mathematical biology, economics, and environmental research. A number of methods for inferring causal relationships within complex dynamic and stochastic systems have been proposed, but there is not a unified consistent definition of causality in the context of time series data. We evaluate the performance of ten prominent causality indices for bivariate time series across four simulated model systems that have different coupling schemes and characteristics. Pairwise correlations between different methods, averaged across all simulations, show that there is generally strong agreement between methods, with minimum, median, and maximum Pearson correlations between any pair (excluding two similarity indices) of 0.298, 0.719, and 0.955, respectively. In further experiments, we show that these methods are not always invariant to real-world relevant transformations (data availability, standardization and scaling, rounding errors, missing data, and noisy data). We recommend transfer entropy and nonlinear Granger causality as particularly strong approaches for estimating bivariate causal relationships in real-world applications. Both successfully identify causal relationships and a lack thereof across multiple simulations, while remaining robust to rounding errors, at least 20% missing data and small variance Gaussian noise. Finally, we provide flexible open-access Python code for computation of these methods and for the model simulations.

DeepClean: Self-Supervised Artefact Rejection for Intensive Care Waveform Data Using Deep Generative Learning.

Waveform physiological data are important in the treatment of critically ill patients in the intensive care unit. Such recordings are susceptible to artefacts, which must be removed before the data can be reused for alerting or reprocessed for other clinical or research purposes. Accurate removal of artefacts reduces bias and uncertainty in clinical assessment, as well as the false positive rate of ICU alarms, and is therefore a key component in providing optimal clinical care. In this work, we present DeepClean, a prototype self-supervised artefact detection system using a convolutional variational autoencoder deep neural network that avoids costly and painstaking manual annotation, requiring only easily obtained 'good' data for training. For a test case with invasive arterial blood pressure, we demonstrate that our algorithm can detect the presence of an artefact within a 10s sample of data with sensitivity and specificity around 90%. Furthermore, DeepClean was able to identify regions of artefacts within such samples with high accuracy, and we show that it significantly outperforms a baseline principal component analysis approach in both signal reconstruction and artefact detection. DeepClean learns a generative model and therefore may also be used for imputation of missing data.

meaRtools: An R package for the analysis of neuronal networks recorded on microelectrode arrays.

Here we present an open-source R package 'meaRtools' that provides a platform for analyzing neuronal networks recorded on Microelectrode Arrays (MEAs). Cultured neuronal networks monitored with MEAs are now being widely used to characterize in vitro models of neurological disorders and to evaluate pharmaceutical compounds. meaRtools provides core algorithms for MEA spike train analysis, feature extraction, statistical analysis and plotting of multiple MEA recordings with multiple genotypes and treatments. meaRtools functionality covers novel solutions for spike train analysis, including algorithms to assess electrode cross-correlation using the spike train tiling coefficient (STTC), mutual information, synchronized bursts and entropy within cultured wells. Also integrated is a solution to account for bursts variability originating from mixed-cell neuronal cultures. The package provides a statistical platform built specifically for MEA data that can combine multiple MEA recordings and compare extracted features between different genetic models or treatments. We demonstrate the utilization of meaRtools to successfully identify epilepsy-like phenotypes in neuronal networks from Celf4 knockout mice. The package is freely available under the GPL license (GPL> = 3) and is updated frequently on the CRAN web-server repository. The package, along with full documentation can be downloaded from: https://cran.r-project.org/web/packages/meaRtools/.